Abstract
The retinal degeneration slow (rds/rds) mouse was used to test photoreceptor protection by systemic gene delivery of non-erythropoietic forms of erythropoietin (EPO). Two Epo mutants were generated and packaged into recombinant adeno-associated virus (rAAV) serotype 2/5, controls included rAAV2/5.Epo and rAAV2/5.enhanced green fluorescent protein (eGFP). Mice were injected in the quadriceps at postnatal day seven and analyses were performed at postnatal day 90. Hematocrit, serum EPO levels, and outer nuclear layer (ONL) thickness were quantified. Hematocrit and serum EPO levels in rAAV2/5.eGFP, rAAV2/5.Epo, and rAAV2/5.EpoR103E treated mice were: 46%, 8 mU/ml; 63%, 117 mU/ml; and 52%, 332 mU/ml, respectively. The ONL from rds/rds mice treated with the Epo vectors were approximately twice as thick as the negative controls. This demonstrates that the photoreceptors can be protected without performing an intraocular injection and without increasing the hematocrit to unsafe levels. Intramuscular delivery of rAAV.EpoR103E is an attractive treatment for retinal degenerative diseases.
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Acknowledgments
This project was funded by grants to T.S.R. from The Roche Foundation for Anemia Research, Hope for Vision, and UTHSC Neuroscience Institute. Additional support was provided by an unrestricted grant from Research Prevent Blindness and an NEI Core Grant 5P30EY13080.
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Special Issue: In Honor of Dr. Dianna Johnson.
An erratum to this article can be found at http://dx.doi.org/10.1007/s11064-012-0785-2
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Sullivan, T., Kodali, K. & Rex, T.S. Systemic Gene Delivery Protects the Photoreceptors in the Retinal Degeneration Slow Mouse. Neurochem Res 36, 613–618 (2011). https://doi.org/10.1007/s11064-010-0272-6
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DOI: https://doi.org/10.1007/s11064-010-0272-6